Supplementary file 1_Targeting heparanase-associated epithelial glycocalyx remodeling attenuates Akt/NF-κB–related barrier dysfunction in experimental COPD.docx

In the murine COPD model, CV122 treatment significantly improved pulmonary function, reduced inflammatory cytokine production, and attenuated emphysematous and fibrotic remodeling. Mechanistically, CV122 preserved epithelial glycocalyx integrity, restored the expression and localization of ZO-1, occludin, and E-cadherin, and reduced epithelial and vascular permeability. In addition, CV122 inhibited Akt and NF-κB pathway activation, accompanied by decreased levels of TNF-α, IL-1β, and IL-6.

Consistently, CV122 protected BEAS-2B cells against CSE-induced apoptosis, cytotoxicity, inflammatory responses, and barrier dysfunction.</p>Conclusion<p>This study identifies HPSE-associated glycocalyx remodeling as an important contributor to epithelial barrier dysfunction in COPD. Pharmacological inhibition of HPSE with CV122 preserves glycocalyx integrity, restores epithelial barrier function, and attenuates inflammatory signaling, at least in part through suppression of the Akt/NF-κB pathway.

These findings advance our understanding of glycocalyx remodeling in COPD and support HPSE as a promising therapeutic target for disease modification.</p>